Toxic epidermal necrolysis and Stevens-Johnson syndrome

Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP), disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS). Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease

IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis

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Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity

Cutaneous adverse reactions are reported for many treatments including antiosteoporotic agents. This position paper includes an algorithm for their recognition. With early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration, and systemic corticosteroids, if necessary, the prognosis is good. Cutaneous adverse reactions are reported for many therapeutic agents and observed in between 0% and 8% of treated patients depending on the drug. The antiosteoporotic agents are reputed to be safe in terms of cutaneous effects; however, there have been a number of case reports of cutaneous adverse reactions, which merit consideration. This was the subject of a Working Group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, to focus on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. We prepared this position paper following these discussions, and include an algorithm for their recognition. We reviewed cutaneous adverse reactions observed with antiosteoporotic agents, including information from case reports, regulatory documents, and pharmacovigilance. The cutaneous adverse reactions range from benign reactions including exanthematous or maculopapular eruption (drug rash), photosensitivity, and urticaria to the severe and potentially life-threatening reactions, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Review of available evidence shows that cutaneous adverse reactions occur with all commonly used antiosteoporotic agents. Notably, there are reports of SJS and TEN for bisphosphonates, and of DRESS and TEN for strontium ranelate. These severe reactions remain very rare (< 1 in 10,000 cases). With early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization and rehydration and systemic corticosteroids if necessary, the prognosis is good